TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9

doi:10.1038/s41586-020-2282-0

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2282-0
	TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9
	Kokail, C.; Maier, C.; van Bijnen, R.; Brydges, T.; Joshi, M. K.; Jurcevic, P.; Muschik, C. A.; Silvi, P.; Blatt, R.; Roos, C. F.; Zoller, P.
	2020-04-03
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	581 期号:7808 页码:316-+
文章类型	Article
语种	英语
国家	Austria; USA
英文关键词	The interaction between TASL and SLC15A4 links endolysosomal Toll-like receptors to the transcription factor IRF5, providing a mechanistic explanation for the involvement of the complex in systemic lupus erythematosus. Toll-like receptors (TLRs) have a crucial role in the recognition of pathogens and initiation of immune responses(1-3). Here we show that a previously uncharacterized protein encoded by CXorf21-a gene that is associated with systemic lupus erythematosus(4,5)-interacts with the endolysosomal transporter SLC15A4, an essential but poorly understood component of the endolysosomal TLR machinery also linked to autoimmune disease(4,6-9). Loss of this type-I-interferon-inducible protein, which we refer to as ' TLR adaptor interacting with SLC15A4 on the lysosome' (TASL), abrogated responses to endolysosomal TLR agonists in both primary and transformed human immune cells. Deletion of SLC15A4 or TASL specifically impaired the activation of the IRF pathway without affecting NF-kappa B and MAPK signalling, which indicates that ligand recognition and TLR engagement in the endolysosome occurred normally. Extensive mutagenesis of TASL demonstrated that its localization and function relies on the interaction with SLC15A4. TASL contains a conserved pLxIS motif (in which p denotes a hydrophilic residue and x denotes any residue) that mediates the recruitment and activation of IRF5. This finding shows that TASL is an innate immune adaptor for TLR7, TLR8 and TLR9 signalling, revealing a clear mechanistic analogy with the IRF3 adaptors STING, MAVS and TRIF10,11. The identification of TASL as the component that links endolysosomal TLRs to the IRF5 transcription factor via SLC15A4 provides a mechanistic explanation for the involvement of these proteins in systemic lupus erythematosus(12-14).
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000532688300007
WOS关键词	INTERFERON REGULATORY FACTOR ; MASS-SPECTROMETRY ; DENDRITIC CELLS ; IKK-BETA ; INNATE ; SLC15A4 ; AUTOIMMUNITY ; PATHOGENESIS ; EXPRESSION ; INSIGHTS
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281461
专题	地球科学资源环境科学气候变化
推荐引用方式 GB/T 7714	Kokail, C.,Maier, C.,van Bijnen, R.,et al. TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9[J]. NATURE,2020,581(7808):316-+.
APA	Kokail, C..,Maier, C..,van Bijnen, R..,Brydges, T..,Joshi, M. K..,...&Zoller, P..(2020).TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9.NATURE,581(7808),316-+.
MLA	Kokail, C.,et al."TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9".NATURE 581.7808(2020):316-+.